In our analysis of older patients with MBC, we found that the average outpatient cancer-related encounter days were 41 days during the first 12 months of initiation of MBC treatment. The finding that older age was not associated with the number of encounter days suggests that other factors, particularly the presence of medical comorbidities, and the type of treatment, played a more significant role in influencing the time burden associated with cancer treatment toxicity.
The most time-intensive outpatient visits were laboratory and diagnostic testing which were significantly more intensive in older adults (67–69 year old) as compared to the very old (80 + year old). A prior study had reported physical or clinical assessments to be a time-intensive activity costing the patients 4hrs/month. [13] A study focusing on patients with early-stage breast cancer revealed an average of 44 outpatient encounter days over an 18-month period. This finding prompts an interesting comparison to our study, especially considering that our study population entirely comprised of patients with MBC.[14, 15] Another study reported an average of 9·9 outpatient visits in the first 12 months for patients with MBC but it excluded testing and imaging encounters which explains the significant contrast to our findings.21
The relation between comorbidity burden and time toxicity is consistent with findings from a prior study among patients with pancreatic ductal adenocarcinoma.[16] This suggests that patients with pre-existing comorbidities may encounter greater challenges during cancer treatments leading to more time toxicity due to their baseline health status. Additionally, treatment protocols for older patients often focus more on oral therapies and avoid intensive therapies such as chemotherapy due to the convenience and flexibility in the administration process.[17] Our study did not include oral therapies administered at home, as their contribution to time toxicity is limited.[13, 18, 19] Less intensive treatment is commonly received by very old patients, because of factors such as prevalence of comorbidities, lower life expectancy, and increased risk of adverse effects contributing to the perception that multi-modal treatments may be less favorable for this patient population, as well as patient preference and shared decision making .[20, 21] This preference as well as more frequent dose reductions may contribute to the observed disappearance of the age-time toxicity association in the multivariable analysis after adjustment for key clinical confounders.
We further stratified outpatient visits and found that chemotherapy and radiotherapy contributed the most towards the total cancer-related encounter days. Patients in the youngest age category of older adults (67–69 years) spent more time receiving treatment than their oldest counterparts (80 + years). These results are congruent with prior findings wherein the estimated time spent was the highest for patients with MBC receiving weekly infusions of chemotherapy.[22] Other studies among patients with pancreatic adenocarcinomas also found that patients lost the most amount of time seeking chemotherapy (10% of their overall survival days).[8, 16] The National Comprehensive Cancer Network’s survey reported the average patient wait time in infusion centers to range from 25 to 102 minutes with a high degree of variation for the same chemotherapy regimens.[23] This can prolong wait times and worsen time-related toxicity. Furthermore, the general shortage of oncology nurses might also contribute to delays in infusions.[24–26] Thus, higher time toxicity might be associated with the type of treatment and the efficiency with which it is administered.
Our study also revealed that patients with MBC spent roughly 18% of the total cancer-related encounter days (11.7 ± 24.58 days) hospitalized during the first year of treatment initiation. This duration was higher compared to previous studies on MBC (6·4–9·3 days) and non-small-cell lung cancer patients (9 days).[10, 18, 22] It is important to note that these studies did not capture the hospitalizations throughout the entire year following treatment initiation.[22] Yet our finding that outpatient visits are a prominent contributor to the number of encounter days is notable, given that prior work suggests that patients with MBC spent an average of 220 minutes at a typical clinical encounter.[22, 27] Thus, considering outpatient care is vital in evaluating the impact of cancer treatment on patients and identifying sources of time toxicities, as it plays a significant role in their overall care experience.
A considerable surge in cancer incidence in the US is projected among its aging population, with over 70% of cancer patients being aged 65 years or older.[28] There are a wide variety of guideline-based treatment options available to patients with MBC, along with different treatment logistics that can be tailored to their individual preferences.[22, 29] Furthermore, existing tools like Comprehensive Geriatric Assessment (CGA) help evaluate the medical, psychological and functional capabilities of these patients, assisting healthcare providers gain a deeper understanding of their health status, comorbidities and overall capacity to withstand various treatments.[30] By gaining insights into patients' preferences and incorporating time toxicities during CGA, healthcare providers can modify treatment guidelines and practice provisions to develop a time-efficient Oncology Care Model for older adults with cancer and facilitate shared decision-making choosing treatments that are truly congruent with the goals of care. Our study is novel in that it investigates and compares time toxicities between old and very old patients with MBC and reaffirms that medical comorbidities are major contributors to increased time toxicity independent of age.
There are several limitations of this study. First, we have not considered factors such as time spent in nursing/rehabilitation facilities, home-based care, tele-health appointments, traveling for appointments, coordinating care, or time spent by caregivers, which are essential for a comprehensive assessment of time toxicities. This was an inherent limitation of the retrospective SEER-Medicare database. Clinical trials present a promising opportunity to gather data on time toxicity; however, clinical trial populations differ substantially from and are generally healthier than real-world populations and the trial protocol itself may be more time-consuming than standard-of-care.[31, 32] Second, the time toxicities associated with individual treatment types are not mutually exclusive and may underestimate the associated time toxicities due to the overlap of patients receiving multiple forms of treatments. Moreover, our analysis doesn't rule out the significance and clinical consequences of reducing or delaying cancer treatment doses, which is more common in older patients at higher risk, potentially lowering side effects and related complications. Future studies can focus on time toxicities associated with individual treatment regimens as these might be informative for comparative research.[32, 33] Third, our measure of time toxicity does not take into account the duration of healthcare contact, which can range from minutes to hours spent in a day.[34] An all-encompassing measure of time toxicity may not adequately capture the experiences and sources of toxicity that may differ for patients based on their socioeconomic status, race, age, and access to resources. Therefore, relying solely on a single overall time toxicity number may be misleading.